A primary role of the thyroid cell is to synthesize and secrete thyroid hormones, thyroxine and triiodothyronine. Taking into consideration the variable intake of iodide, this conversion process is accomplished in a regulated manner and involves numerous steps: concentrated uptake of iodide from the bloodstream across the basal membrane of the cell vectorial transport of iodide through the cell, efflux of iodide across the apical membrane into the lumen of the thyroid follicle; synthesis of thyroglobulin, vectorial transport of thyroglobulin to the follicular lumen; iodination of thyroglobulin,; regulated storage of iodinated thyroglobulin; resorption into the cell; and degradation with reutilization of the iodine and secretion of thyroid hormones into the bloodstream. This process is further regulated by hormones including thyrotropin (TSH), adrenergic agents, insulin, cortisol, insulin-like growth factors, and iodine itself. These hormonal influences regulate the mary steps described above and these processes have been the focus of some of our work over several years. My work continues to focus or transport proteins involved in the uptake as well as the efflux of iodide in the thyroid. My work characterizes the properties of this transport and the hormones and agents that influence, regulate or block these processes. A third direction we are pursuing is the iodinated intermediates between iodide and thyroid hormones mentioned above. This work includes the chemical modification of thyroglobulin as a means of understanding the role of hormone-rich iodopeptides in the synthesis and release of thyroid hormones from thyroglobulin. The work is being focussed at present on the thyroglobulin from patients with endemic goiter, a condition where in the absence of nutritional iodide, the thyroid compensates both in the size and function of the gland to provide the essential thyroid hormones. Over 400 million individuals worldwide are at risk of illness resulting from iodine deficiency. The work continues to investigate the role of ion fluxes as important early events in the action of hormones, as well as the complex pathway of iodine metabolism in the synthesis and release of thyroid hormones in normal function and pathology of the thyroid.